Inversion of helicity has long intrigued investigators in a number of fields (Pijper & Feringa, Angew. Chem. Int'l Ed. 46:3693 (2007); Maeda et al., J. Am. Chem. Soc'y 128:7639 (2006); Sakurai et al., J. Am. Chem. Soc'y 128:5650 (2006); Canary et al., Coord. Chem. Rev. 254:2249 (2010)). In synthetic chemistry, interesting studies have included the employment of single enantiomer ligands with different solvents (Seerden et al., Tetrahedron: Asymmetry 6:1441 (1995); Seerden et al., Tetrahedron Lett. 35:4419 (1994); Seerden et al., Tetrahedron 53:11843 (1997); Sohtome et al., Angew. Chem. Int'l Ed. 49:9254 (2010)), counterions (Gothelf et al., J. Org. Chem. 61:346 (1996); Gothelf et al., J. Org. Chem. 63:5483 (1998); Crosignani et al., Tetrahedron 54:15721 (1998); Crosignani et al., Tetrahedron Lett. 40:7007 (1999); Desimoni et al., Tetrahedron 53:7671 (1997)), metals (Kinting et al., J. Organomet. Chem. 370:343 (1989); Ghosh et al., Tetrahedron Lett. 37:3815 (1996); Sibi et al., J. Am. Chem. Soc'y 120:6615 (1998); Yabu et al., J. Am. Chem. Soc'y 123:9908 (2001)), and temperatures (Kanemasa et al., J. Am. Chem. Soc'y 121:8675 (1999)) in an attempt to toggle the enantioselectivity of a reaction, which has enjoyed varying degrees of success (Sibi & Liu, Curr. Org. Chem. 5:719 (2001); Zanoni et al., Chem. Soc'y Rev. 32:115 (2003); Penning & Jez, Chem. Rev. 101:3027 (2001); Tanaka & Hayashi, Synthesis 21:3361 (2008)). Most such systems reported to date have been discovered by serendipity, and rational design of catalysts with ready triggers to modulate or invert enantioselectivity have been elusive. A thiourea organocatalyst employing a phototriggered, helically chiral molecular rotor scaffold was recently designed (Wang & Feringa, Science 331:1429 (2011)). In this system, photoswitching produced thermally interconverting atropisomers that catalyzed the formation of enantiomeric products of the addition of a thiophenol to cyclohexenone. Redox-modulated catalysts have been reported that provide elements of allosteric reactivity control, but no redox-based system has been shown to control enantioselectivity (Slone et al., J. Am. Chem. Soc'y 119:10743 (1997); Gregson et al., J. Am. Chem. Soc'y 128:7410 (2006); Broderick et al., Chem. Commun. 47:9897 (2011); Broderick et al., J. Am. Chem. Soc'y 133:9278 (2011); Lorkovic et al., J. Am. Chem. Soc'y 117:3617 (1995)).
The field of asymmetric catalysis has been a boon towards the synthesis of chiral pharmaceuticals and chiral sensors. All asymmetric catalysts, though, are either directly synthesized from, or are enantiomerically resolved using, chiral natural products. Biological homochirality nearly always results in only one enantiomer or diastereomer in the biosynthetic pathway used to create chiral compounds, which leads to the scarce production of unnatural enantiomers. Predictably, this limits the availability of the catalysts that are derived from naturally disfavored chiral compounds that must be produced by often resource-intensive synthetic routes. The ability to toggle the enantioselectivity of a reaction by using a reconfigurable catalyst could conserve resources and reduce waste in asymmetric catalysis processes by eliminating the need to produce the enantiomer otherwise unavailable from nature's chiral pool.
The present invention is directed to overcoming these and other deficiencies in the art.